INCREASE IN THE EXTRACELLULAR HISTAMINE CONCENTRATION IN THE RAT STRIATUM BY MU-OPIOID RECEPTOR ACTIVATION

The effects of morphine and selective ligands for mu-, kappa-, and delta-opioid receptors on the extracellular histamine (HA) concentration in the striatum of freely moving rats were examined by in vivo microdialysis. On the day after implantation of the dialysis probe, the HA output per 30-min period was measured using HPLC-fluorometry. Morphine (3.8 mg/kg, s.c.) significantly increased the HA output by similar to 200% 1-3 h after treatment. This effect was completely antagonized by naltrexone (1.6 mg/kg, s.c.). The HA output decreased to a level below 10% of the basal value by 4 h after treatment with (S)-alpha-fluoromethylhistidine (77 mg/kg, s.c.). In such animals, morphine (3.8 mg/kg, s.c.) had no influence on the HA output. [D-Ala(2),MePhe(4),Gly(ol)(5)]Enkephalin (DAGO; 0.2 mu g, i.c.v.), a selective mu-agonist, significantly increased the HA output by similar to 150% 0.5-1.5 h after treatment, and this effect was also completely blocked by naltrexone. A selective kappa-agonist, U-50,488 (3.8 and 7.6 mg/kg, s.c.), and a selective delta-agonist, [D-Pen(2),D-Pen(5)]enkephalin (0.5 and 2 mu g, i.c.v.), had no effect on the HA output. These findings suggest that the stimulation of mu-opioid receptors by morphine and DAGO increases the extracellular HA Concentration by accelerating HA release from nerve endings.